High consumption of trans-fatty acids (TFAs) linked with obesity, disorders of lipoproteins, type 2 Diabetes Mellitus (T2DM), risk factors of coronary heart disease, and development of atherosclerosis. The intent of our trials was to assess the possible bad impact of TFAs on the lipid status and focusing on characterizing the physiological alters in an animal model comparing with cis fatty acids. Sixty male albino rats, with nearly similar average weight 170±5wereassignedinto 4 main groups (15 rats per group) and kept on a standard diet set for 12 weeks. All groups received different diet treatment for successive 12 weeks. Group A: control group received a conventional diet, group B received a diet contained 360 gm TFAs inform of partially hydrogenated vegetable oil (PHVO) l kg of diet, group C was fed a High Fat Diet (HFD) contained 360 gm beef tallow l kg of diet for, and group D received a diet containing 360 gm linseed oil l kg of diet. Both feeding of TFAs and HFD resulted in a marked increase in the body weight in reach to the obesity grade with a significant increase (P≤0.05) in leptin and leptin receptor gene expression. Also, a significant increase in Malondialdehyde (MDA) and Lipoprotein-a (Lp-a) and a marked decrease in total antioxidant capacity (TAC). It could be concluded that TFAs induce combined increased body weight, with imbalance in oxidative stress, dyslipidemia, and elevated atherogenic Lipoprotein-a may be leading to development of atherosclerosis and coronary heart disease.